Asymmetric Total Syntheses of (+)-Davisinol and (+)-18-Benzoyldavisinol: A HAT-Initiated Transannular Redox Radical Approach

Abstract

The first and asymmetric total syntheses of two C11-oxygenated hetisine-type diterpenoid alkaloids, namely, (+)-davisinol and (+)-18-benzoyldavisinol, is described. The concise synthetic approach features a HAT-initiated transannular redox radical cyclization, an ODI-Diels–Alder cycloaddition, and an acylative kinetic resolution. By incorporating an efficient late-stage assembly of the azabicycle, our strategy would streamline the synthetic design of C20-diterpenoid alkaloids and pave the way for their modular syntheses.

Cobalt-electrocatalytic HAT for functionalization of unsaturated C–C bonds

“…As e-HAT relies on the in-situ formation of a cobalthydride, chemoselective reactions are thus possible simply by tuning conditions. A similarly broad scope was observed for this isomerization as well (17)(18)(19)(20)(21)(22)(23)(24)(25). The ability to achieve olefin isomerizations in the presence of free phenols, pyridines, anilines, nitriles, and epoxides is without precedent.…”

“…18 Given the growing documented utility of such reactions in organic synthesis, it is clear that more practical and universal variants are needed. 19,20 In parallel, the same types of species have been efficiently and sustainably generated in the hydrogen production field with a proton as the hydride source (Figure 1B). 2 For example, hydrogen evolution via electrochemically generated Co-H species was known as early as 1985.…”

Recent advances in total synthesis of natural products by masked ortho‐benzoquinones

“…Ding and co-workers reported asymmetric total syntheses of (+)-davisinol and (+)-18-benzoyldavisinol through an IMDA reaction of MOB 50, followed by a hydrogen atom transfer (HAT)-initiated transannular redox radical approach to construct tricyclo[4.3.1.0 3,7 ]decane (Scheme 7). [13] Through cyclohexanone 48, enantioenriched 2-methoxyphenol 49 was obtained in six steps including acylative kinetic resolution. Oxidative dearomatization of 2-methoxyphenol 49 generated MOB 50, and followed by a diastereoselective IMDA reaction to yield endo-adduct 51 in situ.…”

Divergent Total Syntheses of Napelline-Type C20-Diterpenoid Alkaloids: (−)-Napelline, (+)-Dehydronapelline, (−)-Songorine, (−)-Songoramine, (−)-Acoapetaldine D, and (−)-Liangshanone

“…These intriguing structural features rendered these C 20 -diterpenoid alkaloids challenging and attractive targets for synthetic chemists . During the past decades, remarkable achievements have been accomplished toward accessing ent -atisane diterpene-derived alkaloids such as atisines, hetidines, hetisines, denudatines, and arcutines . However, there has been limited success in the total synthesis of the ent -kaurenoid alkaloids. , …”